Search

Your search keyword '"Yeung, Jennifer"' showing total 286 results
Start Over Author "Yeung, Jennifer"
286 results on '"Yeung, Jennifer"'

2. Fatty acids negatively regulate platelet function through formation of noncanonical 15‐lipoxygenase‐derived eicosanoids

Author

Yamaguchi, Adriana, Hoorebeke, Christopher, Tourdot, Benjamin E, Perry, Steven C, Lee, Grace, Rhoads, Nicole, Rickenberg, Andrew, Green, Abigail R, Sorrentino, James, Yeung, Jennifer, Freedman, J Cody, Holman, Theodore R, and Holinstat, Michael

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Clinical Research, Cardiovascular, Fatty Acids, Oxylipins, Arachidonate 15-Lipoxygenase, Eicosanoids, Lipoxygenase Inhibitors, Scavenger Receptors, Class E, 15-lipoxygenase, lipoxygenase, platelet, Medicinal and Biomolecular Chemistry, Pharmacology and pharmaceutical sciences
Abstract

The antiplatelet effect of polyunsaturated fatty acids is primarily attributed to its metabolism to bioactive metabolites by oxygenases, such as lipoxygenases (LOX). Platelets have demonstrated the ability to generate 15-LOX-derived metabolites (15-oxylipins); however, whether 15-LOX is in the platelet or is required for the formation of 15-oxylipins remains unclear. This study seeks to elucidate whether 15-LOX is required for the formation of 15-oxylipins in the platelet and determine their mechanistic effects on platelet reactivity. In this study, 15-HETrE, 15-HETE, and 15-HEPE attenuated collagen-induced platelet aggregation, and 15-HETrE inhibited platelet aggregation induced by different agonists. The observed anti-aggregatory effect was due to the inhibition of intracellular signaling including αIIbβ3 and protein kinase C activities, calcium mobilization, and granule secretion. While 15-HETrE inhibited platelets partially through activation of peroxisome proliferator-activated receptor β (PPARβ), 15-HETE also inhibited platelets partially through activation of PPARα. 15-HETrE, 15-HETE, or 15-HEPE inhibited 12-LOX in vitro, with arachidonic acid as the substrate. Additionally, a 15-oxylipin-dependent attenuation of 12-HETE level was observed in platelets following ex vivo treatment with 15-HETrE, 15-HETE, or 15-HEPE. Platelets treated with DGLA formed 15-HETrE and collagen-induced platelet aggregation was attenuated only in the presence of ML355 or aspirin, but not in the presence of 15-LOX-1 or 15-LOX-2 inhibitors. Expression of 15-LOX-1, but not 15-LOX-2, was decreased in leukocyte-depleted platelets compared to non-depleted platelets. Taken together, these findings suggest that 15-oxylipins regulate platelet reactivity; however, platelet expression of 15-LOX-1 is low, suggesting that 15-oxylipins may be formed in the platelet through a 15-LOX-independent pathway.

Published
2023

5. Omega-6 DPA and its 12-lipoxygenase–oxidized lipids regulate platelet reactivity in a nongenomic PPARα-dependent manner

Author

Yeung, Jennifer, Adili, Reheman, Yamaguchi, Adriana, Freedman, Cody J, Chen, Angela, Shami, Ryan, Das, Aditi, Holman, Theodore R, and Holinstat, Michael

Subjects
Medical Biochemistry and Metabolomics, Biomedical and Clinical Sciences, Hematology, Nutrition, Complementary and Integrative Health, Prevention, Clinical Research, Cardiovascular, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Animals, Arachidonate 12-Lipoxygenase, Blood Platelets, Lipids, Mice, PPAR alpha, Peroxisome Proliferators, Cardiovascular medicine and haematology
Abstract

Arterial thrombosis is the underlying cause for a number of cardiovascular-related events. Although dietary supplementation that includes polyunsaturated fatty acids (PUFAs) has been proposed to elicit cardiovascular protection, a mechanism for antithrombotic protection has not been well established. The current study sought to investigate whether an omega-6 essential fatty acid, docosapentaenoic acid (DPAn-6), and its oxidized lipid metabolites (oxylipins) provide direct cardiovascular protection through inhibition of platelet reactivity. Human and mouse blood and isolated platelets were treated with DPAn-6 and its 12-lipoxygenase (12-LOX)-derived oxylipins, 11-hydroxy-docosapentaenoic acid and 14-hydroxy-docosapentaenoic acid, to assess their ability to inhibit platelet activation. Pharmacological and genetic approaches were used to elucidate a role for DPA and its oxylipins in preventing platelet activation. DPAn-6 was found to be significantly increased in platelets following fatty acid supplementation, and it potently inhibited platelet activation through its 12-LOX-derived oxylipins. The inhibitory effects were selectively reversed through inhibition of the nuclear receptor peroxisome proliferator activator receptor-α (PPARα). PPARα binding was confirmed using a PPARα transcription reporter assay, as well as PPARα-/- mice. These approaches confirmed that selectivity of platelet inhibition was due to effects of DPA oxylipins acting through PPARα. Mice administered DPAn-6 or its oxylipins exhibited reduced thrombus formation following vessel injury, which was prevented in PPARα-/- mice. Hence, the current study demonstrates that DPAn-6 and its oxylipins potently and effectively inhibit platelet activation and thrombosis following a vascular injury. Platelet function is regulated, in part, through an oxylipin-induced PPARα-dependent manner, suggesting that targeting PPARα may represent an alternative strategy to treat thrombotic-related diseases.

Published
2020

6. More Than 50 Percent Reduction in LDL Cholesterol in Patients With Target LDL <70 mg/dL After a Stroke

Author

Amarenco, Pierre, Lavallée, Philippa C., Kim, Jong S., Labreuche, Julien, Charles, Hugo, Giroud, Maurice, Lee, Byung-Chul, Mahagne, Marie-Hélène, Meseguer, Elena, Nighoghossian, Norbert, Steg, Philippe Gabriel, Vicaut, Éric, Bruckert, Eric, Kim, Jong S, Touboul, Pierre-Jean, Leys, Didier, Béjot, Yannick, Pico, Fernando, Touzé, Emmanuel, Ducrocq, Gregory, Abtan, Jérémy, Varenne, Olivier, Touboul, Pierre-Jean, Kemmel, Agnes, Syana, Fausta, Ledra, Manele, Nagasara, Tharani, Ledjeroud, Mervette, Samia, Bahous, Hadia, Hafirassou, Hazare, Benyoub, Jaghouni, Ikrame El, Yelles, Nessima, Zemouri, Sofia, Ladjeroud, Mervette, Kerai, Salim, In, YunJeong, Hobeanu, Cristina, Guidoux, Celine, Cabrejo, Lucie, Lapergue, Bertrand, Sabben, Candice, Gonzalez-Valcarcel, Jaime, Rigual, Ricardo, Sirimarco, Gaia, Martin-Bechet, Anna, Viedma, Elena, Avram, Ioan, Samson, Yves, Rosso, Charlotte, Crozier, Sophie, Leder, Sara, Léger, Anne, Deltour, Sandrine, Mutlu, Gurkan, Yger, Marion, Zavanone, Chiara, Baronnet, Flore, Pires, Christine, Lapergue, Bertrand, Wang, Adrien, Evrard, Serge, Tchikviladze, Maya, Bourdain, Frédéric, Lopez, Delphine, Pico, Fernando, de la Tour, Laetitia Bayon, Chadenat, Marie-Laure, Duong, Duc Long, Genty, Solène, Hirel, Catherine, Mutlu, Gurkan, Nifle, Chantal, Servan, Jérôme, Stanciu, Daniela, Sudacevschi, Veronica, Tir, Mélissa, Troussière, Anne-Cécile, Yeung, Jennifer, Zeghoudi, Anne-Céline, Tidafi-Bayou, Ikram, Lachaud, Sylvain, Cho, Tae-Hee, Mechtouff, Laura, Ritzenthaller, Thomas, Derex, Laurent, Albanesi, Carlo, Ong, Elodie, Benoit, Amandine, Berhoune, Nadia, Felix, Sandra, Esteban-Mader, Maud, Sibon, Igor, Kazadi, Annabelle, Rouanet, François, Renou, Pauline, Debruxelles, Sabrina, Poli, Mathilde, Sagnier, Sharmila, Mas, Jean-Louis, Domigo, Valérie, Lamy, Catherine, Bodiguel, Eric, Grimaud, Jérôme, Bohotin, Valentin, Obadia, Michael, Sabben, Candice, Morvan, Erwan, Rodier, Gilles, Vadot, Wilfried, Hénon, Hilde, Cordonnier, Charlotte, Dumont, Frédéric, Bodenant, Marie, Lucas, Christian, Moulin, Solène, Dequatre, Nelly, Alamowitch, Sonia, Muresan, Jean-Paul, Drouet, Thomas, Gallea, Magalie, Dalloz, Marie-Amélie, Delorme, Stephen, Yger, Marion, Béjot, Yannick, Loisel, Philippe, Bonnin, Carine, Bernigal, Virginie, Osseby, Guy Victor, Hervieu-BègueMarsac, Marie, Garnier, Pierre, Accassat, Sandrine, Epinat, Magali, Varvat, Jérôme, Marinescu, Doïna, Triquenot-Bagan, Aude, Ozkul- Wermester, Ozlem, Philippeau, Frédéric, Olaru, Angel, Vieillart, Anne, Lannuzel, Annie, Demoly, Alice, Wolff, Valérie, Diaconu, Mihaela, Bataillard, Marc, Montoro, Francisco Macian, Faugeras, Frédéric, Gimenez, Laeticia, Abdallah-Lebeau, Françoise, Timsit, Serge, Viakhireva-Dovganyuk, Irina, Tirel-Badets, Anne, Merrien, François-Mathias, Goas, Philippe, Rouhart, François, Jourdain, Aurore, Guillon, Benoit, Hérissson, Fanny, Sevin-Allouet, Mathieu, Nasr, Nathalie, Olivot, Jean-Marc, Lecluse, Alderic, Marc, Guillaume, Touzé, Emmanuel, de la Sayette, Vincent, Apoil, Marion, Lin, Li, Cogez, Julien, Guettier, Sophie, Godefroy, Olivier, Lamy, Chantal, Bugnicourt, Jean-Marc, Taurin, Grégory, Mérienne, Marc, Gere, Julien, Chessak, Anne-Marie, Habet, Tarik, Ferrier, Anna, Bourgois, Nathalie, Minier, Dominique, Caillier-Minier, Marie, Contégal- Callier, Fabienne, Vion, Philippe, Vaschalde, Yvan, Amrani, Mohammed El, Emilie, Zuber, Mathieu, Bruandet, Marie, Join- Lambert, Claire, Garcia, Pierre-Yves, Serre, Isabelle, Faucheux, Jean-Marc, Radji, Fatia, Leca-Radu, Elena, Debroucker, Thomas, Cumurcuc, Rodica, Cakmak, Serkan, Peysson, Stéphane, Ellie, Emmanuel, Bernady, Patricia, Moulin, Thierry, Montiel, Paola, Revenco, Eugeniu, Decavel, Pierre, Medeiros, Elisabeth, Bouveret, Myriam, Louchart, Pierre, Vaduva, Claudia, Couvreur, Grégory, Sartori, Eric, Carpentier, Alnajar, Levasseur, Michèle, Louchart, Pierre, Faucheux, Jean-Marc, Neau, Philippe, Vandamme, Xavier, Meresse, Isabelle, Stantescu, Bataillard, Marc, Ozsancak, Canan, Beauvais, Katell, Auzou, Pascal, Amevigbe, Joséphine, Vuillemet, Francis, Dugay-Arentz, Marie-Hélène, Carelli, Gabriela, Martinez, Mikel, Maillet-Vioud, Marcel, Escaillas, Jean-Pierre, Chapuis, Stéphane, Tardy, Jean, Manchon, Eric, Varnet, Olivier, Kim, Yong-Jae, Chang, Yoonkyung, Song, Tae-Jin, Kim, Jong Sung, Han, Jung-Hoon, Noh, Kyung Chul, Lee, Eun-Jae, Kang, Dong-Wha, Kwon, Sun Uck, Kwon, Boseoung, Park, Seongho, Lee, Dongwhane, Kwon, Hyuk Sung, Jeong, Daeun, Lee, MinHwan, Kim, Joonggoo, Lee, Hanbin, Nam, Hyo Jung, Lee, Sang Hun, Kim, Bum Joon, Cha, Jae-kwan, Kim, DaeHyun, Kim, Rae Young, Sohn, Sang Wuk, Shim, Dong-Hyun, Lee, Hyungjin, Nah, Hyun-Wook, Sung, Sang Min, Lee, Kyung Bok, Yoon Lee, Jeong, Yoon, Jee Eun, Kim, Eung-Gyu, Seo, Jung Hwa, Kim, Yong-Won, Hwang, Yangha, Park, Man Seok, Kim, Joon-Tae, Choi, Kang-Ho, Nam, Hyo Suk, Heo, Ji Hoe, Kim, Young Dae, Hwang, In Gun, Park, Hyung Jong, Kim, Kyoung Sub, Baek, Jang Hyun, Song, Dong Beom, Yoo, Joon Sang, Park, Jong-Moo, Kwon, Ohyun, Lee, Woong-Woo, Lee, Jung-Ju, Kang, Kyusik, Kim, Byung Kun, Lim, Jae-Sung, Oh, Mi Sun, Yu, Kyung-Ho, Hong, Bora, Jang, Mihoon, Jang, Seyoung, Jin, Jung Eun, Kim, Jei, Jeong, Hye Seon, Hong, Keun Sik, Park, Hong Kyun, Cho, Yong Jin, Bang, Oh Young, Seo, Woo-Keun, and Chung, Jongwon

Published
2023
Full Text
View/download PDF

10. First Selective 12-LOX Inhibitor, ML355, Impairs Thrombus Formation and Vessel Occlusion In Vivo With Minimal Effects on Hemostasis.

Author

Adili, Reheman, Tourdot, Benjamin, Mast, Katherine, Yeung, Jennifer, Freedman, John, Green, Abigail, Luci, Diane, Jadhav, Ajit, Simeonov, Anton, Maloney, David, Holinstat, Michael, and Holman, Ted|Theodore

Subjects
collagen, hemostasis, lipoxygenase, platelet reactivity, thrombosis, Animals, Dose-Response Relationship, Drug, Hemostasis, Humans, Lipoxygenase Inhibitors, Mice, Platelet Adhesiveness, Platelet Aggregation, Sulfonamides, Thrombin, Thrombosis
Abstract

OBJECTIVE: Adequate platelet reactivity is required for maintaining hemostasis. However, excessive platelet reactivity can also lead to the formation of occlusive thrombi. Platelet 12(S)-lipoxygenase (12-LOX), an oxygenase highly expressed in the platelet, has been demonstrated to regulate platelet function and thrombosis ex vivo, supporting a key role for 12-LOX in the regulation of in vivo thrombosis. However, the ability to pharmacologically target 12-LOX in vivo has not been established to date. Here, we studied the effect of the first highly selective 12-LOX inhibitor, ML355, on in vivo thrombosis and hemostasis. APPROACH AND RESULTS: ML355 dose-dependently inhibited human platelet aggregation and 12-LOX oxylipin production, as confirmed by mass spectrometry. Interestingly, the antiplatelet effects of ML355 were reversed after exposure to high concentrations of thrombin in vitro. Ex vivo flow chamber assays confirmed that human platelet adhesion and thrombus formation at arterial shear over collagen were attenuated in whole blood treated with ML355 comparable to aspirin. Oral administration of ML355 in mice showed reasonable plasma drug levels by pharmacokinetic assessment. ML355 treatment impaired thrombus growth and vessel occlusion in FeCl3-induced mesenteric and laser-induced cremaster arteriole thrombosis models in mice. Importantly, hemostatic plug formation and bleeding after treatment with ML355 was minimal in mice in response to laser ablation on the saphenous vein or in a cremaster microvasculature laser-induced rupture model. CONCLUSIONS: Our data strongly support 12-LOX as a key determinant of platelet reactivity in vivo, and inhibition of platelet 12-LOX with ML355 may represent a new class of antiplatelet therapy.

Published
2017

11. Same-Day Discharge is Safe, Feasible Following Vaginal Hysterectomy with Apical Suspension

Author

Ray,Marlana, Yeung,Jennifer, Hoehn,Jonathan, Valenti,Matthew, Lewis,Kelsey, Pauls,Rachel, Crisp,Catrina, Ray,Marlana, Yeung,Jennifer, Hoehn,Jonathan, Valenti,Matthew, Lewis,Kelsey, Pauls,Rachel, and Crisp,Catrina

Abstract

Marlana M Ray,1 Jennifer Yeung,1 Jonathan Hoehn,2 Matthew Valenti,3 Kelsey E Lewis,1 Rachel N Pauls,1 Catrina C Crisp1 1Urogynecology Division, TriHealth, Cincinnati, OH, USA; 2Hatton Research Institute, TriHealth, Cincinnati, OH, USA; 3OB/GYN Department, University of Cincinnati, Cincinnati, OH, USACorrespondence: Marlana M Ray, TriHealth, Urogynecology Division, 3219 Clifton Ave, Medical Office Building Suite 100, Cincinnati, OH, 45220, USA, Email marlana_ray@trihealth.comPurpose: Studies involving minimally invasive hysterectomy and robotic sacrocolpopexy have demonstrated safety and feasibility of same-day discharge. There are limited data, however, on same-day discharge outcomes for vaginal hysterectomy and pelvic reconstruction. This study aimed to compare 30 and 90-day surgical outcomes between same-day discharge versus overnight stay following vaginal hysterectomy and apical suspension.Patients and Methods: This retrospective study evaluated surgeries performed over two time periods. Overnight stay was standard between December 2018 and February 2020. Same-day discharge was standard from December 2020 to February 2022. All patients who underwent vaginal hysterectomy with apical suspension were included. The primary outcome was to determine if there was an increase in 30-day readmission rates. Secondary outcomes included emergency department visits and reoperations within 30 days, the previous variables at 90 days, and the rate for successful same-day discharge.Results: A total of 324 patients were analyzed over the 30 months: 149 (46%) in the overnight stay group and 175 (54%) in the same-day discharge group. At 30 days, no difference was found between groups for readmissions (2.7% vs 4.0%, p = 0.56), emergency department visits (14.8% vs 14.9%, p = 1.0), or reoperations (2.0% vs.1.7%, p = 1.0). At 90 days, outcomes were also similar. Same-day discharge as standard practice was successful in 80% of patients.Conclusion: In this retrospective two cohort study

Published
2024

13. 12(S)-HETrE, a 12-Lipoxygenase Oxylipin of Dihomo-&ggr;-Linolenic Acid, Inhibits Thrombosis via G&agr;s Signaling in Platelets

Author

Yeung, Jennifer, Tourdot, Benjamin E, Adili, Reheman, Green, Abigail R, Freedman, Cody J, Fernandez-Perez, Pilar, Yu, Johnny, Holman, Theodore R, and Holinstat, Michael

Subjects
Medical Physiology, Biomedical and Clinical Sciences, Nutrition, Hematology, Cardiovascular, Clinical Research, Prevention, Aetiology, 2.1 Biological and endogenous factors, Blood, 8, 11, 14-Eicosatrienoic Acid, Animals, Arachidonate 12-Lipoxygenase, Blood Platelets, Cell Adhesion Molecules, Chromogranins, Cyclic AMP, Cyclic AMP-Dependent Protein Kinases, Disease Models, Animal, Fibrinolytic Agents, GTP-Binding Protein alpha Subunits, Gs, Humans, Mice, Inbred C57BL, Mice, Knockout, Microfilament Proteins, Oxidation-Reduction, Phosphoproteins, Phosphorylation, Platelet Activation, Platelet Aggregation, Platelet Aggregation Inhibitors, Shelterin Complex, Signal Transduction, Telomere-Binding Proteins, Thrombosis, Time Factors, blood platelets, eicosanoids, fibrin, lipoxygenase, platelet activation, thrombosis, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract

ObjectiveDietary supplementation with polyunsaturated fatty acids has been widely used for primary and secondary prevention of cardiovascular disease in individuals at risk; however, the cardioprotective benefits of polyunsaturated fatty acids remain controversial because of lack of mechanistic and in vivo evidence. We present direct evidence that an omega-6 polyunsaturated fatty acid, dihomo-γ-linolenic acid (DGLA), exhibits in vivo cardioprotection through 12-lipoxygenase (12-LOX) oxidation of DGLA to its reduced oxidized lipid form, 12(S)-hydroxy-8Z,10E,14Z-eicosatrienoic acid (12(S)-HETrE), inhibiting platelet activation and thrombosis.Approach and resultsDGLA inhibited ex vivo platelet aggregation and Rap1 activation in wild-type mice, but not in mice lacking 12-LOX expression (12-LOX(-/-)). Similarly, wild-type mice treated with DGLA were able to reduce thrombus growth (platelet and fibrin accumulation) after laser-induced injury of the arteriole of the cremaster muscle, but not 12-LOX(-/-) mice, supporting a 12-LOX requirement for mediating the inhibitory effects of DGLA on platelet-mediated thrombus formation. Platelet activation and thrombus formation were also suppressed when directly treated with 12(S)-HETrE. Importantly, 2 hemostatic models, tail bleeding and arteriole rupture of the cremaster muscle, showed no alteration in hemostasis after 12(S)-HETrE treatment. Finally, the mechanism for 12(S)-HETrE protection was shown to be mediated via a Gαs-linked G-protein-coupled receptor pathway in human platelets.ConclusionsThis study provides the direct evidence that an omega-6 polyunsaturated fatty acid, DGLA, inhibits injury-induced thrombosis through its 12-LOX oxylipin, 12(S)-HETrE, which strongly supports the potential cardioprotective benefits of DGLA supplementation through its regulation of platelet function. Furthermore, this is the first evidence of a 12-LOX oxylipin regulating platelet function in a Gs α subunit-linked G-protein-coupled receptor-dependent manner.

Published
2016

14. Platelet 12-LOX is essential for FcγRIIa-mediated platelet activation

Author

Yeung, Jennifer, Tourdot, Benjamin E, Fernandez-Perez, Pilar, Vesci, Joanne, Ren, Jin, Smyrniotis, Christopher J, Luci, Diane K, Jadhav, Ajit, Simeonov, Anton, Maloney, David J, Holman, Theodore R, McKenzie, Steven E, and Holinstat, Michael

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Hematology, Cardiovascular, Clinical Research, Blood, 12-Hydroxy-5, 8, 10, 14-eicosatetraenoic Acid, Animals, Arachidonate 12-Lipoxygenase, Blood Platelets, Calcium, Enzyme Activation, Humans, Mice, Mice, Inbred C57BL, Mice, Transgenic, Phospholipase C gamma, Phosphorylation, Platelet Activation, Platelet Aggregation, Protein Kinase C, Receptors, IgG, Signal Transduction, Thrombosis, Cardiorespiratory Medicine and Haematology, Clinical Sciences, Paediatrics and Reproductive Medicine, Immunology, Biochemistry and cell biology, Cardiovascular medicine and haematology, Paediatrics
Abstract

Platelets are essential in maintaining hemostasis following inflammation or injury to the vasculature. Dysregulated platelet activity often results in thrombotic complications leading to myocardial infarction and stroke. Activation of the FcγRIIa receptor leads to immune-mediated thrombosis, which is often life threatening in patients undergoing heparin-induced thrombocytopenia or sepsis. Inhibiting FcγRIIa-mediated activation in platelets has been shown to limit thrombosis and is the principal target for prevention of immune-mediated platelet activation. In this study, we show for the first time that platelet 12(S)-lipoxygenase (12-LOX), a highly expressed oxylipin-producing enzyme in the human platelet, is an essential component of FcγRIIa-mediated thrombosis. Pharmacologic inhibition of 12-LOX in human platelets resulted in significant attenuation of FcγRIIa-mediated aggregation. Platelet 12-LOX was shown to be essential for FcγRIIa-induced phospholipase Cγ2 activity leading to activation of calcium mobilization, Rap1 and protein kinase C activation, and subsequent activation of the integrin αIIbβ3. Additionally, platelets from transgenic mice expressing human FcγRIIa but deficient in platelet 12-LOX, failed to form normal platelet aggregates and exhibited deficiencies in Rap1 and αIIbβ3 activation. These results support an essential role for 12-LOX in regulating FcγRIIa-mediated platelet function and identifies 12-LOX as a potential therapeutic target to limit immune-mediated thrombosis.

Published
2014

16. Investigations of human platelet-type 12-lipoxygenase: role of lipoxygenase products in platelet activation 1 [S]

Author

Ikei, Kenneth N, Yeung, Jennifer, Apopa, Patrick L, Ceja, Jesús, Vesci, Joanne, Holman, Theodore R, and Holinstat, Michael

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Clinical Research, Hematology, Arachidonate 12-Lipoxygenase, Fatty Acids, Essential, Humans, Oxidation-Reduction, Platelet Activation, Substrate Specificity, thrombin, fatty acid oxidation, eicosanoids, thrombosis, Medical Biochemistry and Metabolomics, Biochemistry & Molecular Biology, Biochemistry and cell biology, Medical biochemistry and metabolomics
Abstract

Human platelet-type 12-lipoxygenase (12-LOX) has recently been shown to play an important role in regulation of human platelet function by reacting with arachidonic acid (AA). However, a number of other fatty acids are present on the platelet surface that, when cleaved from the phospholipid, can be oxidized by 12-LOX. We sought to characterize the substrate specificity of 12-LOX against six essential fatty acids: AA, dihomo-γ-linolenic acid (DGLA), eicosapentaenoic acid (EPA), α-linolenic acid (ALA), eicosadienoic acid (EDA), and linoleic acid (LA). Three fatty acids were comparable substrates (AA, DGLA, and EPA), one was 5-fold slower (ALA), and two showed no reactivity with 12-LOX (EDA and LA). The bioactive lipid products resulting from 12-LOX oxidation of DGLA, 12-(S)-hydroperoxy-8Z,10E,14Z-eicosatrienoic acid [12(S)-HPETrE], and its reduced product, 12(S)-HETrE, resulted in significant attenuation of agonist-mediated platelet aggregation, granule secretion, αIIbβ3 activation, Rap1 activation, and clot retraction. Treatment with DGLA similarly inhibited PAR1-mediated platelet activation as well as platelet clot retraction. These observations are in surprising contrast to our recent work showing 12(S)-HETE is a prothrombotic bioactive lipid and support our hypothesis that the overall effect of 12-LOX oxidation of fatty acids in the platelet is dependent on the fatty acid substrates available at the platelet membrane.

Published
2012

17. Protein Kinase C Regulation of 12-Lipoxygenase-Mediated Human Platelet Activation

Author

Yeung, Jennifer, Apopa, Patrick L, Vesci, Joanne, Kenyon, Victor, Rai, Ganesha, Jadhav, Ajit, Simeonov, Anton, Holman, Theodore R, Maloney, David J, Boutaud, Olivier, and Holinstat, Michael

Subjects
Biochemistry and Cell Biology, Medical Physiology, Biomedical and Clinical Sciences, Biological Sciences, Hematology, Clinical Research, Cardiovascular, 2.1 Biological and endogenous factors, Aetiology, Arachidonate 12-Lipoxygenase, Blood Platelets, Blotting, Western, Calcium, Enzyme Activation, Flow Cytometry, Gas Chromatography-Mass Spectrometry, Humans, Lipoxygenase Inhibitors, Platelet Activation, Platelet Glycoprotein GPIIb-IIIa Complex, Protein Kinase C, Protein Kinase Inhibitors, Neurosciences, Pharmacology and Pharmaceutical Sciences, Pharmacology & Pharmacy, Biochemistry and cell biology, Pharmacology and pharmaceutical sciences
Abstract

Platelet activation is important in the regulation of hemostasis and thrombosis. Uncontrolled activation of platelets may lead to arterial thrombosis, which is a major cause of myocardial infarction and stroke. After activation, metabolism of arachidonic acid (AA) by 12-lipoxygenase (12-LOX) may play a significant role in regulating the degree and stability of platelet activation because inhibition of 12-LOX significantly attenuates platelet aggregation in response to various agonists. Protein kinase C (PKC) activation is also known to be an important regulator of platelet activity. Using a newly developed selective inhibitor for 12-LOX and a pan-PKC inhibitor, we investigated the role of PKC in 12-LOX-mediated regulation of agonist signaling in the platelet. To determine the role of PKC within the 12-LOX pathway, a number of biochemical endpoints were measured, including platelet aggregation, calcium mobilization, and integrin activation. Inhibition of 12-LOX or PKC resulted in inhibition of dense granule secretion and attenuation of both aggregation and αIIbβ(3) activation. However, activation of PKC downstream of 12-LOX inhibition rescued agonist-induced aggregation and integrin activation. Furthermore, inhibition of 12-LOX had no effect on PKC-mediated aggregation, indicating that 12-LOX is upstream of PKC. These studies support an essential role for PKC downstream of 12-LOX activation in human platelets and suggest 12-LOX as a possible target for antiplatelet therapy.

Published
2012

19. Benefit of Targeting a LDL (Low-Density Lipoprotein) Cholesterol <70 mg/dL During 5 Years After Ischemic Stroke

Author

Amarenco, Pierre, Kim, Jong S., Labreuche, Julien, Charles, Hugo, Giroud, Maurice, Lee, Byung-Chul, Mahagne, Marie-Hélène, Nighoghossian, Norbert, Gabriel Steg, Philippe, Vicaut, Éric, Bruckert, Eric, Touboul, Pierre-Jean, Leys, Didier, Béjot, Yannick, Lavallée, Philippa, Pico, Fernando, Touzé, Emmanuel, Ducrocq, Gregory, Abtan, Jérémy, Varenne, Olivier, Touboul, Pierre-Jean, Kemmel, Agnes, Syana, Fausta, Ledra, Manele, Nagasara, Tharani, Ledjeroud, Mervette, Samia, Bahous, Hadia, Hafirassou, Hazare, Benyoub, El Jaghouni, Ikrame, Yelles, Nessima, Zemouri, Sofia, Ladjeroud, Mervette, Kerai, Salim, In, Yun Jeong, Meseguer, Elena, Lavallée, Philippa C, Hobeanu, Cristina, Guidoux, Celine, Cabrejo, Lucie, Lapergue, Bertrand, Sabben, Candice, Gonzalez-Valcarcel, Jaime, Rigual, Ricardo, Sirimarco, Gaia, Martin-Bechet, Anna, Viedma, Elena, Avram, Ioan, Samson, Yves, Rosso, Charlotte, Crozier, Sophie, Leder, Sara, Léger, Anne, Deltour, Sandrine, Mutlu, Gurkan, Yger, Marion, Zavanone, Chiara, Baronnet, Flore, Pires, Christine, Lapergue, Bertrand, Wang, Adrien, Evrard, Serge, Tchikviladze, Maya, Bourdain, Frédéric, Lopez, Delphine, Pico, Fernando, de la Tour, Laetitia Bayon, Chadenat, Marie-Laure, Duong, Duc Long, Genty, Solène, Hirel, Catherine, Mutlu, Gurkan, Nifle, Chantal, Servan, Jérôme, Stanciu, Daniela, Sudacevschi, Veronica, Tir, Mélissa, Troussière, Anne-Cécile, Yeung, Jennifer, Zeghoudi, Anne-Céline, Tidafi-Bayou, Ikram, Lachaud, Sylvain, Cho, Tae-Hee, Mechtouff, Laura, Ritzenthaller, Thomas, Derex, Laurent, Albanesi, Carlo, Ong, Elodie, Benoit, Amandine, Berhoune, Nadia, Felix, Sandra, Esteban-Mader, Maud, Sibon, Igor, Kazadi, Annabelle, Rouanet, François, Renou, Pauline, Debruxelles, Sabrina, Poli, Mathilde, Sagnier, Sharmila, Mas, Jean-Louis, Domigo, Valérie, Lamy, Catherine, Bodiguel, Eric, Grimaud, Jérôme, Bohotin, Valentin, Obadia, Michael, Sabben, Candice, Morvan, Erwan, Rodier, Gilles, Vadot, Wilfried, Hénon, Hilde, Cordonnier, Charlotte, Dumont, Frédéric, Bodenant, Marie, Lucas, Christian, Moulin, Solène, Dequatre, Nelly, Alamowitch, Sonia, Muresan, Jean-Paul, Drouet, Thomas, Gallea, Magalie, Dalloz, Marie-Amélie, Delorme, Stephen, Yger, Marion, Béjot, Yannick, Loisel, Philippe, Bonnin, Carine, Bernigal, Virginie, Osseby, Guy Victor, Marsac, Marie Hervieu-Bègue, Garnier, Pierre, Accassat, Sandrine, Epinat, Magali, Varvat, Jérôme, Marinescu, Doïna, Triquenot-Bagan, Aude, Ozkul-Wermester, Ozlem, Philippeau, Frédéric, Olaru, Angel, Vieillart, Anne, Lannuzel, Annie, Demoly, Alice, Wolff, Valérie, Diaconu, Mihaela, Bataillard, Marc, Montoro, Francisco Macian, Faugeras, Frédéric, Gimenez, Laeticia, Abdallah-Lebeau, Françoise, Timsit, Serge, Viakhireva-Dovganyuk, Irina, Tirel-Badets, Anne, Merrien, François-Mathias, Goas, Philippe, Rouhart, François, Jourdain, Aurore, Guillon, Benoit, Hérissson, Fanny, Sevin-Allouet, Mathieu, Nasr, Nathalie, Olivot, Jean-Marc, Lecluse, Alderic, Marc, Guillaume, Touzé, Emmanuel, de la Sayette, Vincent, Apoil, Marion, Lin, Li, Cogez, Julien, Guettier, Sophie, Godefroy, Olivier, Lamy, Chantal, Bugnicourt, Jean-Marc, Taurin, Grégory, Mérienne, Marc, Gere, Julien, Chessak, Anne-Marie, Habet, Tarik, Ferrier, Anna, Bourgois, Nathalie, Minier, Dominique, Caillier-Minier, Marie, Contégal-Callier, Fabienne, Vion, Philippe, Vaschalde, Yvan, El Amrani, Emilie, Mohammed, Zuber, Mathieu, Bruandet, Marie, Join-Lambert, Claire, Garcia, Pierre-Yves, Serre, Isabelle, Faucheux, Jean-Marc, Radji, Fatia, Leca-Radu, Elena, Debroucker, Thomas, Cumurcuc, Rodica, Cakmak, Serkan, Peysson, Stéphane, Ellie, Emmanuel, Bernady, Patricia, Moulin, Thierry, Montiel, Paola, Revenco, Eugeniu, Decavel, Pierre, Medeiros, Elisabeth, Bouveret, Myriam, Louchart, Pierre, Vaduva, Claudia, Couvreur, Grégory, Sartori, Eric, Alnajar-Carpentier, Eric, Levasseur, Michèle, Louchart, Pierre, Neau, Jean-Philippe, Vandamme, Xavier, Meresse, Isabelle, Stantescu, Bataillard, Marc, Ozsancak, Canan, Beauvais, Katell, Auzou, Pascal, Amevigbe, Joséphine, Vuillemet, Francis, Dugay-Arentz, Marie-Hélène, Carelli, Gabriela, Martinez, Mikel, Maillet-Vioud, Marcel, Escaillas, Jean-Pierre, Chapuis, Stéphane, Tardy, Jean, Manchon, Eric, Varnet, Olivier, Kim, Yong-Jae, Chang, Yoonkyung, Song, Tae-Jin, Han, Jung-Hoon, Noh, Kyung Chul, Lee, Eun-Jae, Kang, Dong-Wha, Kwon, Sun Uck, Kwon, Boseoung, Park, Seongho, Lee, Dongwhane, Kwon, Hyuk Sung, Jeong, Daeun, Lee, MinHwan, Kim, Joonggoo, Lee, Hanbin, Nam, Hyo Jung, Lee, Sang Hun, Kim, Bum Joon, Cha, Jae-kwan, Kim, DaeHyun, Young Kim, Rae, Sohn, Sang Wuk, Shim, Dong-Hyun, Lee, Hyungjin, Nah, Hyun-Wook, Sung, Sang Min, Lee, Kyung Bok, Lee, Jeong Yoon, Yoon, Jee Eun, Kim, Eung-Gyu, Seo, Jung Hwa, Kim, Yong-Won, Hwang, Yangha, Park, Man Seok, Kim, Joon-Tae, Choi, Kang-Ho, Nam, Hyo Suk, Heo, Ji Hoe, Kim, Young Dae, Hwang, In Gun, Park, Hyung Jong, Kim, Kyoung Sub, Baek, Jang Hyun, Song, Dong Beom, Yoo, Joon Sang, Park, Jong-Moo, Kwon, Ohyun, Lee, Woong-Woo, Lee, Jung-Ju, Kang, Kyusik, Kim, Byung Kun, Lim, Jae-Sung, Oh, Mi Sun, Yu, Kyung-Ho, Hong, Bora, Jang, Mihoon, Jang, Seyoung, Jin, Jung Eun, Kim, Jei, Jeong, Hye Seon, Hong, Keun Sik, Park, Hong Kyun, Cho, Yong Jin, Bang, Oh Young, Seo, Woo-Keun, and Chung, Jongwon

Published
2020
Full Text
View/download PDF

23. Efficacy of Endovascular Therapy in Acute Ischemic Stroke Depends on Age and Clinical Severity

Author

Le Bouc, Raphaël, Clarençon, Frédéric, Meseguer, Elena, Lapergue, Bertrand, Consoli, Arturo, Turc, Guillaume, Naggara, Olivier, Duong, Duc Long, Servan, Jerome, Reiner, Peggy, Labeyrie, Marc Antoine, Fisselier, Mathieu, Blanc, Raphaël, Farhat, Wassim, Pires, Christine, Zuber, Mathieu, Obadia, Michael, Mazighi, Mikael, Pico, Fernando, Mas, Jean-Louis, Amarenco, Pierre, Samson, Yves, Rosso, Charlotte, Crozier, Sophie, Deltour, Sandrine, Leger, Anne, Baronnet, Flore, Frasca-Polara, Giulia, Diaz, Belen, Sourour, Nader, Di Maria, Frederico, Pistocchi, Silvia, Bartolini, Bruno, Hobeanu, Christina, Rigual, Ricardo, Guidoux, Céline, Cabrejo, Lucie, Lavallée, Philippa, Martin-Bechet, Anna, Sabben, Candice, Bourdain, Frédéric, Wang, Adrien, Evrard, Serge, Decroix, Jean-Pierre, Tchikviladze, Maya, Tisserand, Marie, Rodesch, Georges, Coskun, Oguzhan, Seners, Pierre, Isabel, Clothilde, Lamy, Catherine, Domigo, Valérie, Birchenall, Julia, Guiraud, Vincent, Bodiguel, Eric, Calvet, David, Trystram, Denis, Rodriguez-Régent, Christine, Ben Hassen, Wagih, Boulouis, Grégoire, Godon-Hardy, Sylvie, Méder, Jean-François, Oppenheim, Catherine, Zeghoudi, Anne-Cécile, Nifle, Chantal, Yeung, Jennifer, Stanciu, Daniela, Buch, Dan, Chadenat, Marie-Laure, Girbovan, Aandrei, Bayon, Laeticia, Troussiere, Anne-Cécile, Calinescu, Georgina, Rostomashvili, Sophio, SudaveschiVeronica, de Malherbe, Maxime, Chabriat, Hugues, Jouvent, Eric, Herve, Dominique, Porcher, Frédérique, Bouquet-Castiglione, Floriane, Morvan, Typhaine, Lyoubi-Idrissi, Aïcha, Cognat, Emmanuel, Join Lambert, Claire, Tamazyan, Ruben, and Gerber, Sophie

Published
2018
Full Text
View/download PDF

30. Contributors

Author

Abel, Dori, Abelman, Rebecca A., Abu Kar, Sarah, Abughazaleh, Saeed, Abu-Nejim, Husam, Afari, Maxwell Eyram, Ahmed, Hammood, Akoto, Shanice, Alabre, Kenneth, Ali, Fahad, Ali, Tanya, Alipanah-Lechner, Narges, Altunel, Erdem, Alzoebie, Lama, Anderson, Chelsie, Andrews, Christine B., Anthony, AnnGene, Arcand, Paul-Hugo, Arora, Sohrab, Asaro, Joseph A., Astashchanka, Anna, Atchison, Douglas, Aulakh, Sudeep K., Aurora, Taruna, Avasare, Rupali, Babadi, Baktash, Babar, Tania B., Bachman, Emelia Argyropoulos, Bains, Ashika, Balabanov, Roumen, Balaguera, Pedro, Balda, Javier, Bank, T. Caroline, Banwell, Brenda, Barrera, Francisco J., Barta, Samantha, Basman, Craig L., Bass, Crystal T., Beach, Scott R., Bediako, Persey, Belcher, Ren, Bell, Jennifer, Bellinghausen, Amy L., Bennett, Colleen E., Berkowitz, Carol D., Betageri, Omkar, Bharmal, Murtaza, Bhatt, Harikrashna B., Bhuptani, Prachi H., Bido-Medina, Richard O., Bielak, Kendall, Bilodeau, Courtney Clark, Bird, Lisa, Bishop, Erin, Bitar, Ghamar, Blakeney, Craig, Blatz, Allison M., Block, Brian, Bortz, Christina M., Bosse, Kristopher R., Bouton, Tara C., Bove, Mary E., Bowlby, Lynn A., Boyden, Sean, Brady, Mark F., Braide, Biobele, Brar, Jessica K., Bratman, Russell E., Brodowsky, Emily Chan, Brown, Austin K., Brown, Emily C.B., Brugnoni, Jessalyn, Bui, Eric, Burke, Christine, Burton, Lauren, Butler, Blythe, Butler, William, Byanova, Katerina L., Byg, Blaire, Callanan, Tucker C., Cantos, Adriana, Canty, Katherine W., Carragee, Eugene, Carrel-Lammert, Meredith, Castillo, Jorge J., Chait, Daniel, Chan, Philip A., Chapman, Arlene, Chatterjee-Paer, Sudeshna, Cheng, Vicky, Chien, Michael, Chilcote, Jeffrey, II, Childs, Candicee, Chopra, Amit, Chou, Stella T., Choudhury, Natasha, Christian, Cindy W., Chua, Winona, Chun, Andrew S., Claman, David, Clark, Grace V., Clark, Seth, Clarke, Ross, Clay, Alexandra, Clebak, Karl T., Cleland, Derrick, Cohen, Debbie L., Cohen, Lisa, Congdon, Morgan, Constantinou, Maria, Cooper, James Elliott, Corley, James Earl, Cosgrove, Abigail, Covarrubias, Oscar, Craine, Rebecca, Criddle, Sarah, Cristofaro, Patricia, Cunha, Joanne Szczygiel, Cunningham, Karlene, Cusano, Joseph, D’Alessandro, Frank B., Dado, Lynn, Daneshdoost, Shanaz, Daneshvari, Nicholas Omid, Darwiche, Sabrina, Das, Abhijit, DaSilva, Manuel F., De La Garza, Carlos, DeDent, Alison, Deeb, Mery, Denninger, John W., Desrochers, Colette, Devon, Erin Pete, Diaz, Joseph A., DiGrande, Kyle, Dina, Ayodeji, Doo, Kathleen, Drury, Brian, Dus, Bethany, Dutta, Roop, Dworkin, Myles, Dyster, Timothy G., Ebert, Eric, Edmund, Joseph, Edward, Heather L., Eggers, Erica, Eisenhower, Christine, Ellsworth, Pamela, Elnair, Radowan, Escamilla-Ocañas, César E., Espinosa, Patricio Sebastian, Faber, Mark D., Facer, Evan, Fadale, Paul D., Fallon, Ryan T., Farias, Michael J., Farkas, Jon, Farrand, Erica, Farrell, Ronan, Fay, Kevin S., Fender, Robert Zachary, Hernandez, Samantha Fernandez, Fernandez-Robles, Carlos, Ferreira, Jason D., Ferri, Fred F., Ferri, Heather, Fields, Jessica C., Fields, Lauren, Fischer, Staci A., Fiske, Hannah, Florez, Maria Camila Velez, Forbes, Kellie C., Forcier, Michelle, Ford, Sydney, Fort, Frank G., Fort, Glenn G., Frankel, Eitan S., Freeman, Nancy, Friedman, Ryan, Frisch, Daniel R., Fru, Relindis Azenwi, Fullenkamp, Lynn C., Gaffney, Michael, Garcia, Jose P., Garcia, Paloma Jolin, Ge, Jonathan S., Gesthalter, Yaron B., Ghimire, Anil, Gibson, Christopher, Gidwani, Nisha H., Gilek-Seibert, Katarzyna, Gilvaz, Vinit J., Glueck, Jacob, Goetz, Jennifer Leah, Goldburt, Alla, Goldsmith, Corey Elam, Rao Golla, Maheswara Satya Gangadhara, Gomez, Alexander, Slagle, Helen B. Gomez, Greenblatt, H. Karl, Greenfield, Morgan, Gugerty, Lindsay, Gultawatvichai, Patan, Gunning, Samantha, Guo, David, Gupta, Simran, Guttadauria, Brittany, Gwinn, Meghan, Hadi, Mohanad, Hafeez, Muhammad Ubaid, Hall, Hayden, Hall, Sarah, Handa, Sajeev, Hanna, John R., Harbord, Nikolas, Hardacker, Kyle, Hardesty, Anna, Haribhakti, Nirav, Harris, Daniel J., Hartmann, Abigail, Hartnett, Davis A., Hartvigsen, Nathan, Hawkins, Brian, He, Elaine, Heinle, Rachel Wright, Helm, Leesha A., Helm, Matthew F., Herlevich, Thomas, Hermez, Klodia M., Hilliard, Ross W., Hocker, Nathaniel, Hoffman, R. Scott, Holton, Siri M., Homer, Alexander S., Hook, Benjamin E., Hsu, Raymond, Huang, Laurence, Hull, Mariam, Hume, Anne L., Hussain, Zilla, Huynh, Donny V., Hyder, Sarah, Ingraham, Caitlin, Insalaco, Louis F., Jackson, James, Jafari-Esfahani, Shadi, Jain, Rishubh, Jain, Vanita B.D., Jain, Vipul V., Jamal, Fariha, Janigian, Robert H., Jr., Jasuja, Sonia, Javier, Noelle Marie, Jayachandran, Nishant, Jetty, Vybhav, Johnson, Michael P., Johnson, Steven D., Jones, Amanda, Joseph, Tatiana, Joseph-Senatus, Ganaelle, Joshi, Shyam, Justice, Joshua, Kabashneh, Sohaip, Kadiyala, Vishnu, Kalligeros, Markos, Karthikeyan, Vanji, Kaske, Erika, Kasper, Vania, Kass, Joseph S., Kass, Naomi R., Kasthuri, Viknesh S., Katz, Luca, Kazakova, Vera, Keim, Jennifer L., Kensey, Nicholas, Kent, Victoria, Kerrigan, Danielle, Keselman, Dennis, Khare, Sarthak, Khatri, Surya, Khawaja, Hussain R., Khurana, Saranya S., Kifle, Betelhem, Kim, Chan Woo, Kim, Jinseong, Kisare, Samantha, Kohrman, Samuel I., Kokkirala, Aravind Rao, Konstantino, Yuval, Kontos, Nicholas, Kopyt, Nelson, Kothadia, Savan, Koti, Ajay S., Koulouridis, Ioannis, Kreider, Timothy R., Kron, Kevin, Krumm, Ilana, Kuhn, Elizabeth, Kumbar, Lalathaksha, Kuo, Sheng-Han, Kuris, Eren O., Kurss, David I., Kutschke, Michael J., Laband, William F., LaCombe, Philip, Lam, Uyen T., Lam, Wilson, Laredo, Jonathan, Larijani, Mary, Le, Peter, Leahy, Caroline, Leard, Lorriana E., Leavitt, David A., Leba, Christopher T., Lee, Hyung Jin, Lee, Kachiu C., LeGros, Tracy Leigh, Lemme, Nicholas J., L’Etoile, Nathan, Li, Jian, Lim, Carol, Lin, Chi-Ying (Roy), Lippincott, Jordan, Liu, Jonathan, Logue, Teresa C., Longtain, Riley, López, Gabriela, Lord, Kito Akin, Loscalzo, Kirsten, Lucas, Mathew J., Lucier, David J., Jr., Ma’ayeh, Marwan, MacLean, Rachel L., MacMurdo, Maeve G., Madva, Elizabeth N., Maher, Lewena, Makai, Gretchen, Malpica, Luis, Marks, Jonathan, Pinheiro, Ana Paula Marques, Marr, Mollie C., Martinez, Adali, Matin, Adiba, Mazzaglia, Peter J., Mbuyi, Nadine N., McCulloh, Russell J., McDonald-McGinn, Donna M., McGowen, Alexandra, McGraw, Katherine Elizabeth, McKenna, Jaclyn, McNamara, Kelly, Meleveedu, Kapil S., Mendez-Miller, Megan, Mercado, Jorge, Mercado, Osvaldo, Merritt, Rory, Michaels, Marian G., Michel, Jeremy, Mikolasko, Brian D., Milner, John D., Min, May, Minami, Taro, Mohamed, Mouhand F., Najjar-Mojarrab, Javad, Molinari, John, Montgrain, Philippe, Moon, Heesung, Moore, Michael Z., Moore, Shawn D., Morelli, Leah, Morrissey, Patrick J., Mughal, Aleem I., Mukkamalla, Shiva Kumar R., Mullen, Marguerite A., Mulliken, Alexandra, Mumtaz, Tayebah, Muraina, Fadeke, Mustafa, Ahmad, Myers, Ellen, Mylhousen, Emily, Nadaud, Jack, Nadella, Akash, Nadella, Mohnish, Nadjarian, Albert, Nagpal, Nikita, Nathan, Miriam, Naveed, Asim, Nawaiseh, Ahmad Al, Neff, Robert, Neithardt, Adrienne B., Nestlerode, Christina, Niazi, Azfar K., Nisavic, Mladen, Nokoff, Natalie, Noorbhai, Ibrahim Z.D., Novak, James E., Novarra, Austin, John, Audrey R. Odom, Okewunmi, Jeffrey, Oliver, Rebecca, Olszewski, Adam J., Onyeaka, Henry K., Orchowski, Lindsay M., Osorio, Marcela, Osorio, Luis, O’Sullivan, Cassidy, Outlaw, Jasmine, Oyelakin, Ayotomide, Pace, Paolo G., Paddock, John E., Painter, David F., Palmieri, Alicia, Pappas-Taffer, Lisa, Paranandi, Sneha, Parikh, Mihir, Partin, Michael T., Patel, Birju B., Patel, Melissa D., Patel, Minta, Patel, Nima R., Patel, Pranav M., Patel, Vishal I., Patrick, Brett, Paudel, Shreedhar, Pelcovits, Ari, Perez, David L., Perez, Jose J. Hermina, Pétron, Clément, Pfeuti, Courtney, Pham, Lily C., Phillips, Katharine A., Phillips, Oliver W., Phillips, Tara M., Piana, Lauren E., Portnoff, Brandon S., Pou, Sovijja, Prashar, Rohini, Pulice, Christine, Punko, Diana, Purkayastha, Ayan, Qawi, Imrana, Qu, David, Quesada, Adrian, Quinn, Matthew S., Racchi, Nicholas, Rachu, Gregory S., Rajadurai, Suvithan, Ramachandran, Lintu, Rana, Tanvi, Rathore, Bharti, Rathore, Ritesh, Raukar, Neha P., Ravindra, Lakshmi, Reagan, John L., Reardon, P.K., Reddy, Bharathi V., Reddy, Snigdha T., Reed-Weston, Anne, Reginato, Anthony M., Reichart, James P., Reus, Victor I., Reuter, Matthew, Riaz, Sana, Ricci, Brittany, Rich, Harlan G., Richter, Savanah, Rivera, Lauren Davis, Robertson, Melena J., Roby, Lauren C., Roche, Meaghan, Rodriguez, Alejandra E. Morfin, Gómez, Perla M. Romero, Ron, Hayley A., Rossi, Michael, Rubin, David, Rubin, Lila, Rushworth, Parker, Rutstein, Beth H., Sadeghi, Noushine, Sahota, Ruchi Jalota, Saks, Emily, Sall, Jeffrey W., Salvi, Joshua D., Sanchez, Frank A., Sanchez, Martha C., Sanka, Pranavi, Santhosh, Lekshmi, Santos, Linda Herrera, Sauck, Emily, Saylor, Leah, Scheuing, William J., Sciscione, Anthony, Scott, Matthew Thomas, Sederdahl, Bethany K., Seeber, Richard E., II, Sellers, Kyle, Sen, Aritra, Sewell, Rachel, Shaban, Hesham, Shah, Ankur, Shah, Isha, Shakil, Omair, Sharma, Animesh, Sharma, Yuvraj, Sharp, Lydia, Sherman, Alexander, Shill, Jessica E., Shimanovsky, Alexei, Shipp, Michael M., Shlossman, Philip A., Siddiqui, Khawja A., Siegel, Alyssa, Sigman, Mark, Singh, Harinder P., Singh, Jasneet, Singh, Manjot, Slingsby, Brett, Sloane, Amy J., Smick, Alexandra H., Smith, Jeanette G., Smith, Matthew J., Sohaney, Ryann, Soi, Vivek, Soinski, Rebecca, Soler, Maria E., Soman, Sandeep, Sorg, Emily, Sosnoski, Olivia, Sperati, C. John, Stanford, Nathan, Steele, Emery, Steele, Jacqueline, Stern, Ella, Stier, James, Stockwell, Philip, Subramanian, Lakshmi, Suen, Angela, Suh, Edward, Sundaramoorthy, Anjali, Sunkara, Naveena, Supanakorn, Varut, Suri, Priyasha, Sweeney, Hannah, Takasaki, Kaoru, Takei, Ryosuke, Tan, Laren, Tarawneh, Mohammad, Taylor, Alan, Taylor, Kathryn Marie, Taylor, Matthew A., Taylor, S. Trevor, Tenney-Soeiro, Rebecca, Thomas, Anthony G., Thompson, Stefani, Tien, Alexandra Meyer, Tien, David Robbins, Tierney, Anna-Marie, Toma, Helen, Lopez, Kim Tran, Tryforos, Margaret, Tsaban, Gal, Tschoe, Christine, Tungate, Robert, Turn, Christina S., Uduman, Junior, Umanath, Kausik, Ungar, Stephanie P., Vakili, Babak, van Deventer, Ella, Vemula, Ridhima, Venado, Aida, Vollum, Kathryn G., Vorel, Ethan, Walson, Ifeanyi, Wang, Angela, Wang, Emily, Wang, Li, Wehner, Linsey, Westreich, Roi, Wheeler, Ericka, Wighton, Nakia, Wildman, Alexis, Wilson, Annise, Winikor, Jared M., Wininger, Bryce, Winschel, Julia M., Wold, Jaclyn, Wolpaw, Adam J., Wolpert, Marlene Fishman, Wong, Elisabeth A., Wylie, John, Yang, Anna, Yao, Xuan, Yesodharan, Gemini, Yeung, Jennifer, Yin, Chun H., Yip, Agustin G., Yu, Diana H., Yu, Elizabeth An, Yung, Jeffrey, Zainelabdin, Sarah, Zambrano, Juliana, Zargarian, Emin, Zha, B. Shoshana, Zhang, Helen, Zhao, Leon, Zhou, Diana X., Ziaie, Navid, and Zorin, Danylo

Published
2025
Full Text
View/download PDF

39. TRAF6 functions as a tumor suppressor in myeloid malignancies by directly targeting MYC oncogenic activity

Author

Muto, Tomoya, primary, Guillamot, Maria, additional, Yeung, Jennifer, additional, Fang, Jing, additional, Bennett, Joshua, additional, Nadorp, Bettina, additional, Lasry, Audrey, additional, Redondo, Luna Zea, additional, Choi, Kwangmin, additional, Gong, Yixiao, additional, Walker, Callum S., additional, Hueneman, Kathleen, additional, Bolanos, Lyndsey C., additional, Barreyro, Laura, additional, Lee, Lynn H., additional, Greis, Kenneth D., additional, Vasyliev, Nikita, additional, Khodadadi-Jamayran, Alireza, additional, Nudler, Evgeny, additional, Lujambio, Amaia, additional, Lowe, Scott W., additional, Aifantis, Iannis, additional, and Starczynowski, Daniel T., additional

Published
2022
Full Text
View/download PDF

40. Benevolence

Author

Yeung, Jennifer

Abstract

A collection of poems that explores child sexual abuse, state violence, and intra-community connections.

Published
2022
Full Text
View/download PDF

43. Contributors

Author

Abdelazeem, Mohamed A., Abelman, Rebecca A., Kar, Sarah Abu, Afari, Maxwell Eyram, Ahmad, Ali, Ahmed, Hammood, Ahn, Benjamin J., Ahn-Horst, Rosa, Akoto, Shanice, AlAbdulhadi, Abrar, Aldras, Yoseph A., Ali, Fahad, Ali, Tanya, Alipanah-Lechner, Narges, Altunel, Erdem, Alzoebie, Lama, Anderson, Chelsie, Andrews, Christine B., Taylor, Kathryn Maire, Anthony, Anngene, Asaro, Joseph A., Asiedu, Daniel K., Astsaturov, Artem, Aulakh, Sudeep K., Authement, Matthew, Avasare, Rupali S., Babar, Tania B., Bachman, Emelia Argyropoulos, Baig, Muhammad, Bains, Ashika, Balaguera, Pedro, Balda, Javier, Bank, T. Caroline, Banwell, Brenda, Basman, Craig L., Bass, Crystal T., Bayefsky, Sarah D., Beausang, Jasjit, Belcher, Ren, Bell, Jennifer, Bellinghausen, Amy L., Bennett, Colleen E., Benninger, John W., Bergen, Michael A., Berger, Agatha, Berkowitz, Carol D., Berkowitz, Julia, Betageri, Omkar, Bhagat, Vicky H., Bharmal, Murtaza, Bhatt, Harikrashna B., Bhuptani, Prachi H., Bido-Medina, Richard O., Bielak, Kendall M.H., Bilodeau, Courtney Clark, Bird, Lisa, Bishop, Erin, Bitar, Ghamar, Blakeney, Craig, Block, Brian, Bochner, Risa, Bortz, Christina M., Bosse, Kristopher R., Bouton, Tara C., Bove, Mary E., Bowlby, Lynn A., Brady, Mark F., Bratman, Russell E., Brennan, Keith, Brown, Austin K., Brown, Emily C.B., Bui, Eric, Burke, Christine, Butler, William, Byanova, Katerina L., Byra, Marcin, Callanan, Tucker C., Campbell, Taylor, Cantos, Adriana, Canty, Ethan, Canty, Katherine W., Caraganis, Andrew, Carpenter, Randy S., Carragee, Eugene, Carrel-Lammert, Meredith, Carter, Ashlie Sewdass, Casillas, Ernesto, Jr., Castaneda-Guarderas, Ana, Castillo, Jorge J., Chait, Daniel, Chan, Philip A., Chang, Kenny, Chapman, Arlene B., Chatterjee-Paer, Sudeshna, Chaudhary, Richard S., Cheng, Vicky, Chilcote, Daniel, Chofay, Dana Ricci, Chou, Jonathan, Chou, Stella T., Choudhury, Natasha, Choxi, Shivali, Chua, Winona, Chubb, Rhiannon E., Cinelli, Michael P., Claman, David, Clark, Grace V., Clark, Seth, Clarke, Nathan, Clebak, Karl T., Cleland, Derrick, Co, Michael Lawrenz, Cohen, Debbie L., Cohen, Lisa, Congdon, Morgan, Constantinou, Maria, Corley, James Earl, III, Cosgrove, Abigail, Craine, Rebecca, Cristofaro, Patricia, Cruz, Aristides I., Cunningham, Karlene, Curtin, Alicia J., Cusano, Joseph, D’Alessandro, Frank B., Dado, Lynn, Dalela, Deepansh, Das, Abhijit, DaSilva, Manuel F., Davis, Mackenzie, De La Garza, Carlos, DeDent, Alison, Deeb, Maya, DeJong, Tyler, Desrochers, Colette, Diaz, Joseph A., Dickherber, Jason L., Do, Toan, Doo, Kathleen, Dove, James H., Dubanchet, Alexandre, Duh-Leong, Carol, Dutta, Roop, Dworkin, Myles, Dyster, Timothy G., Ebert, Eric, Edmund, Joseph, Eggers, Erica, Eisenhower, Christine, Ellsworth, Pamela, Escamilla-Ocañas, César E., Espinosa, Patricio Sebastian, Esqueda, Marisol, Everly, Eileen, Faber, Mark D., Faber, Rachel, Facer, Evan, Fadale, Paul D., Farahvash, Benyamin, Farias, Michael J., Farkas, Jon, Farrand, Erica, Fay, Kevin, Hernandez, Samantha Fernandez, Fernandez-Robles, Carlos, Ferreira, Jason D., Ferri, Fred F., Ferri, Heather, Fischer, Staci A., Fiske, Hannah, Velez Florez, Maria Camila, Font, Cristina, Forbes, Kellie C., Forcier, Michelle, Ford, Sydney, Fort, Frank G., Fort, Glenn G., Freeman, Nancy, Frisch, Daniel R., Fru, Relindis Azenwi, Fullenkamp, Lynn C., Gaffney, Michael, Garcia, Paloma Jolin, Ge, Connie, Gesthalter, Yaron B., Ghimire, Anil, Gibson, Christopher, Gidwani, Nisha H., Gil, Joseph, Gold, Raphaela, Goldburt, Alla, Goldsmith, Corey Elam, Gangadhara Rao Golla, Maheswara Satya, Gomez, Alexander, Gomez Slagle, Helen B., Greenfield, Morgan, Grisham, Lindsey Anne, Gu, Joey, Guardino, Cara E., Gugerty, Lindsay, Gul, Fahad, Gultawatvichai, Patan, Gunning, Samantha, Guo, Averill, Guo, David, Gupta, Simran, Guttadauria, Brittany, Guzman, Herodes, Gwinn, Meghan, Hadden, Ryan, Hafeez, Muhammad Ubaid, Hall, Hayden, Hall, Sarah, Handa, Sajeev, Handler, Stacy N., Hanna, James, Hanna, John, Harbord, Nikolas, Hardacker, Kyle, Hardesty, Anna, Haribhakti, Nirav, Harris, Daniel J., Hartnett, Davis A., Hartvigsen, Nathan, Hawkins, Brian, Heinle, Rachel Wright, Helm, Leesha A., Helm, Matthew F., Herlevich, Thomas, Hermez, Klodia M., Hilliard, Ross W., Hladky, Katherine, Hodges, Ashley, Hoffman, Ryan, Hoffman, R. Scott, Hogan, Dawn, Holiman, Jennifer J., Holland, N. Wilson, Holton, Siri M., Homer, Benjamin J., Hook, Benjamin E., Howell, Cody, Hsu, Raymond, Huang, Laurence, Hull, Mariam, Hume, Anne L., Hussain, Zilla, Huynh, Donny V., Hyder, Sarah, Ibrahim, Zainab, Ingraham, Caitlin, Inman, Nicholas J., Insalaco, Louis F., Jain, Rishubh, Jain, Vanita B.D., Jain, Vipul V., Jamal, Fariha, Jani, Kaushal, Janigian, Robert H., Jr., Jasuja, Sonia, Javier, Noelle Marie, Jetty, Vybhav, Johnson, Jennie E., Johnson, Michael P., Johnson, Steven D., Jolly, Angad, Jones, Amanda, Joshi, Shyam, Joudi, Kareem, Justice, Joshua, Kaddis, Timothy, Kalligeros, Markos, Karim, Omar, Karthikeyan, Vanji, Kartub, Benjamin, Kasper, Vania, Kass, Joseph S., Kass, Naomi R., Kasthuri, Viknesh S., Katz, Luca, Kaul, Bhavika, Kaur, Arpanjeet, Keim, Jennifer L., Keleshian, Vasken, Keogh, Abigail, Keselman, Dennis, Khan, Adeeba, Khare, Sarthak, Khawaja, Hussain R., Khetpal, Vishal, Khurana, Saranya S., Kifle, Betelhem, Kyung (Ellen) Kim, Eun, Kim, Jinseong, Kleitsch, Julianne, Knudson-Fitzpatrick, Tess, Kohrman, Samuel I., Kokkirala, Aravind Rao, Konstantino, Yuval, Kopyt, Nelson, Kothadia, Savan, Koti, Ajay, Koulouridis, Ioannis, Kreider, Timothy R., Krueger, Van S., Krumm, Ilana, Kumbar, Lalathaksha, Kuris, Eren O., Kurss, David I., L’Etoile, Nathan, Lam, Uyen T., Lam, William, Larijani, Mary, Le, Peter, Leard, Lorriana E., Leavitt, David A., Leba, Christopher T., Lee, Kachiu C., Lemme, Nicholas J., Li, Jian, Lieberman, Leora, Lim, Carol, Lin, Jason, Lippincott, Jordan, Liu, Jonathan, Logue, Teresa C., López, Gabriela, Lord, Kito Akin, Lucas, Mathew J., Lucier, David J., Jr., Ma’ayeh, Marwan, Maclean, Rachel L., MacMurdo, Maeve G., Madva, Elizabeth N., Mahani, Sahar, Makai, Gretchen, Malpica, Luis, Marcaccio, Stephen E., Marques Pinheiro, Ana Paula, Mazzaglia, Peter J., Mbuyi, Nadine N., McCulloh, Russell J., McDonald, Christopher L., McDonald-McGinn, Donna M., McGowen, Alexandra, McGraw, Katherine Elizabeth, McKenna, Jaclyn, McNamara, Kelly, Mead, Kelly C., Meehan, Caroline P., Meghani, Ozair K., Meleveedu, Kapil S., Mendez, Dianelys, Mendez-Miller, Megan, Mercado, Jorge, Mercado, Osvaldo, Merrill, Scott J., Merritt, Rory, Michaels, Marian G., Michel, Jeremy, Mikolasko, Brian D., Milner, John D., Min, May, Minami, Taro, Mitsuyama, Rei, Miyares, Laura, Mogla, Ankur, Mojarrab, Javad Najjar, Montgrain, Philippe, Moore, Michael Z., Moore, Shawn D., Morelli, Leah, Morrissey, Patrick J., Mughal, Aleem I., Mukkamalla, Shiva Kumar R., Mullersman, Katherine M., Mumtaz, Ahmad, Muraina, Fadeke, Mustafa, Ahmad, Myers, Ellen, Mylhousen, Emily, Nadella, Akash, Nadella, Mohnish, Nagpal, Nikita, Nandi, Minesh, Nasir, Uzma, Nasr, George H., Naveed, Asim, Neff, Robert, Neithardt, Adrienne B., Nelin, Timothy, Nestlerode, Christina, Ni, Samantha, Niazi, Azfar K., Nichols, Jonathan, Nokoff, Natalie, Noorbhai, Ibrahim Z.D., Novak, James E., Novarra, Austin, Nuss, Emily E., Oliver, Rebecca, Olszewski, Adam J., Onyeaka, Henry K., Orchowski, Lindsay M., Outlaw, Jasmine, Owens, Brett D., Oyelakin, Ayotomide, Pace, Paolo G., Palma-Zamora, Isaac, Pandya, Rachita, Pappas-Taffer, Lisa, Paranandi, Sneha, Parikh, Mihir, Park, Sara, Partin, Michael T., Patel, Birju B., Patel, Melissa D., Patel, Minta, Patel, Nima R., Patel, Pranav M., Patel, Vidhi, Patrick, Brett, Paudel, Shreedhar, Paxton, E. Scott, Peay, Celeste, Perazella, Mark A., Perez, David L., Hermina Perez, Jose J., Devon, Erin Pete, Pfeuti, Courtney, Pham, Lily C., Phelps-Polirer, Kendall, Phillips, Katharine A., Phillips, Oliver W., Phillips, Tara M., Piana, Lauren E., Portnoff, Brandon, Powell, Mitchell, Powers, Alexander, Prashar, Rohini, Premyodhin, Ned, Price, Dana, Priestley, Margaret, Provenza, Christian, Pulice, Christine, Punko, Diana, Puthawala, Imran, Qawi, Imrana, Qu, David, Quesada, Adrian, Quinn, Matthew, Rachu, Gregory S., Rajagopal, Amulya, Rathore, Bharti, Rathore, Ritesh, Raukar, Neha P., Ravindra, Lakshmi, Reagan, John L., Reardon, P.K., Reddy, Bharathi V., Reddy, Snigdha T., Reed-Weston, Anne, Reginato, Anthony M., Reichart, James P., Reus, Victor I., Rich, Harlan G., Rivera, Lauren Davis, Robertson, Melena J., Roby, Lauren, Roche, Meaghan, Morfin Rodriguez, Alejandra E., Romero Gómez, Perla M., Ron, Hayley A., Rosenbaum, Blake L., Rossi, Michael, Roussel, Breton, Rubin, David, Ruhstaller, Kelly, Rutstein, Beth H., Sadeghi, Noushine, Sahota, Ruchi Jalota, Saks, Emily, Sall, Jeffrey W., Salvi, Joshua D., Sanchez, Frank, Sanchez, Martha C., Sanka, Pranavi, Santhosh, Lekshmi, Santos, Linda Herrera, Sauck, Emily, Sayeed, Syeda M., Saylor, Leah, Schmitt, Phillip R., Sciscione, Anthony, Sederdahl, Bethany K., Seeber, Richard E., II, Sen, Aritra, Sewell, Rachel, Shaban, Hesham, Shah, Ankur, Shaikh, Aaron Ali, Sharma, Animesh, Sharma, Yuvraj, Sharp, Lydia, Sheikh, Wasiq, Sherman, Alexander, Shill, Jessica E., Shimanovsky, Alexei, Shlossman, Philip A., Siddiqui, Khawja A., Siegel, Alyssa, Sigman, Mark, Simon, Rebecca, Singh, Harinder P., Slingsby, Brett, Sloane, Amy, Smick, Alexandra H., Smith, Devon, Smith, Jeanette G., Smith, Matthew J., Sohaney, Ryann, Soi, Vivek, Soinski, Rebecca, Soler, Maria E., Soman, Sandeep, Song, Jeffrey S., Sorg, Emily, Sperati, C. John, Stanford, Nathan, Stennis, Seth Daly, Stephens, Michael S., Stern, Ella, Stockwell, Philip, Suh, Edward, Sun, Jennifer K., Sundaramoorthy, Anjali, Supanakorn, Varut, Suri, Priyasha, Sutter, Stephanie, Sweeney, Hannah, Takasaki, Kaoru, Takei, Ryosuke, Tan, Laren, Taylor, Alan, Taylor, Matthew, Taylor, S. Trevor, Tellioglu, Tahir, Testa, Edward J., Thomas, Anthony G., Thompson, Stefani, Tien, Alexandra Meyer, Tien, David Robbins, Tierney, Anna-Marie, Tiffany, Patrick, Toma, Helen, Triplett, Thomas M., Tryforos, Margaret, Tsaban, Gal, Tschoe, Christine, Tucci, Joseph R., Turock, Julia, Uduman, Junior, Uiterwyk, Sean H., Ukaegbu, Rebecca, Umanath, Kausik, Vakili, Babak, Van Kirk, Emily, Vemula, Ridhima, Venado, Aida, Vijayakumar, Shilpa, Vollum, Kathryn G., Vorel, Ethan, Walson, Ifeanyi, Wang, Angela, Wang, Jarey H., Weekley, Manuel Shayne, Weinberg, Marc S., Wendolowski, Stephen, Westreich, Roi, Whitaker, Colin, Wilhoite, Morgan, Wilks, Andrew, Wilson, Annise, Winikor, Jared M., Wininger, Bryce, Winschel, Julia M., Wolpaw, Adam J., Wolpert, Marlene Fishman, Wu, Perry, Wylie, John, Yaguchi, Grace K., Yang, Anna, Yao, Xuan, Yaseen, Muhammad, Yee, Jerry, Yesodharan, Gemini, Yeung, Jennifer, Yin, Chun H., Yip, Agustin G., Yu, Elizabeth An, Zambrano, Juliana, Zenlea, Talia, Zha, B. Shoshana, Zhang, Helen, Zhao, Leon, Zhou, Diana X., Ziaie, Navid, Zollman, Joshua W., Zorin, Danylo, and Zurek, Olivia

Published
2024
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results